Comparison of long‐term outcomes of laparoscopic and robot‐assisted laparoscopic partial nephrectomy

Abstract

In this study, we compared the long‐term oncological and functional outcomes of laparoscopic partial nephrectomy (LPN) and robot‐assisted laparoscopic partial nephrectomy (RAPN) performed in the treatment of renal tumors. The data of 142 patients (RAPN = 71, LPN = 71) were evaluated. Demographic data, perioperative and postoperative outcomes, long‐term (5‐year) overall survival (OS) and cancer‐specific survival (CSS) rates of the patients were compared between the two groups. A P value of less than 0.05 was considered statistically significant. The mean follow‐up time was 61.38 months. There were more complex tumors in the RAPN group (P = 0.014). The duration of warm ischemia time (WIT) was shorter in the RAPN group (P = 0.019). Perioperative and postoperative outcomes were similar. There were no differences between the groups in terms of 5‐year metastasis‐free survival, OS, and CSS rates. Hypertension, diabetes, and preoperative estimated glomerular filtration rate (eGFR) were the predictive factors for renal insufficiency; and preoperative eGFR, WIT, and positive surgical margin were the predictive factors for 5‐year CSS. We concluded that RAPN is an important minimally invasive treatment method for partial nephrectomy with long‐term favorable results, especially in complex tumors. Comparisons of two methods should be made with comparative, prospective, randomized, high case number studies, and the place of RAPN in the treatment of these tumors should be clarified.

1. INTRODUCTION

Renal cell carcinoma accounts for 2%‐3% of all malignant tumors detected in adults and has the highest mortality rate among the urological cancers.1 The incidence of the disease is increasing with the widespread utilization of ultrasound and other cross‐sectional imaging methods. These methods cause an earlier diagnosis of the disease as well as an increase in the incidence of the disease. It is possible to treat these masses which are diagnosed at an earlier stage and limited to the kidney without causing organ loss by partial nephrectomy (PN). Nowadays, gold standard treatment of localized masses in T1a clinical stage (<4 cm) is partial nephrectomy even in patients with healthy contralateral kidney.2 There has been a shift toward open partial nephrectomy and then laparoscopic (LPN) and robot‐assisted laparoscopic partial nephrectomy (RAPN) from open radical nephrectomy in the treatment of renal tumors over time. Minimally invasive techniques provide better cosmetic results, less postoperative pain, and shorter hospitalization length than open surgery.3

Because of the technical and ergonomic difficulties to perform laparoscopy in a reconstructive operation such as PN, laparoscopy is unfortunately not widely accepted in the treatment of these diseases. LPN is now being performed with highly experienced surgeons and in high case number loaded reference clinics. Robotic surgery has been developed to address this deficit and revolutionized the minimally invasive surgery with the convenience it provides to surgeons. Robotic surgery has also found widespread application in PN (especially for challenging masses such as hilar and endophytic) and it has been reported that RAPN can be successfully applied after performing approximately about 25 cases.4 On the other hand, LPN is a technique that requires a considerable number of cases to complete the long‐learning curve to achieve optimal experience. Instrumentation with limited motion angles makes it very difficult to excise the tumor, ensure the hemostasis, and repair the collecting system and parenchymal defect in the PN.

The extent to which the convenience RAPN provides for the surgeon reflects on the outcome of the disease is already an important debate. Some authors have reported that RAPN provides a shorter warm ischemia time (WIT) than LPN, as well as similar perioperative results with LPN.5, 6 The real superiority of RAPN to LPN is controversial in previously completed comparative studies.5, 6, 7, 8 It is thought that RAPN can improve perioperative and functional outcomes in more complex tumors such as large, hilar, multiple tumors by allowing more competent tumor resection and facilitating reconstructive steps.9

The functional and oncologic results of RAPN and LPN have been studied by a limited number of studies in the literature.10, 11 Undoubtedly, the gold standard studies in this area are randomized controlled studies, but ethical issues, patient preferences, and procedure costs render the execution of these studies quite difficult.

In this study, we present a matched pair comparison of patients treated with RAPN and LPN. We aimed to compare the perioperative and long‐term functional and oncologic results of RAPN and LPN cases since March 2012, when robotic surgery had been initiated in our clinic.

2. MATERIALS AND METHODS

2.1. Patients and measurement methods

A total of 142 patients of which 71 underwent RAPN and 71 LPN between March 2012 and March 2018 in a single center were included in the study. Patient data were retrospectively collected from patient files. The inclusion criteria were renal tumor size ≤7 cm and postoperative follow‐up of at least 6 months. Estimated glomerular filtration rate (eGFR) was calculated preoperatively and postoperatively on 12th months and annually thereafter. eGFR was calculated using the abbreviated Modification of the Kidney Diet Disease Study Group.12 Patients with a renal surgery history, who had an eGFR <15 mL/min/1.73 m², who underwent “zero ischemia” (off‐clamp or segmental artery clamp) and underwent radical nephrectomy or open surgery were excluded.

Tumor size was calculated based on the longest tumor diameter on the axial plane in cross‐sectional imaging. In cross‐sectional view, according to the distance from the kidney surface tumors, >60% were classified as exophytic, <40% as endophytic, between 40%‐60% as mesophytic, and near 5 mm to the renal vessels as hilar renal tumors. Patients’ renal functions were classified according to the National Kidney Foundation Kidney Disease Outcome Quality Initiative Classification.13 Surgical method was decided after exchange of opinions between surgeon and patient. The definition of positive surgical margin (PSM) was based on the detection of tumor cells in the surgical resection area. Informed and written consent was obtained from all patients before the procedures.

2.2. The application of surgical techniques

2.2.1. Robot‐assisted LPN

A 16 Fr foley and a nasogastric catheter were introduced following general anesthesia. Then, in the lumbotomy position, the veress needle was inserted through the palmar region and pneumoperitoneum was created. Two 12‐inch, two 8‐inch robotic ports and one 5‐inch port were inserted. A transperitoneal approach was used for RAPN. After docking, the colon was medialized and the retroperitoneal area was accessed. The ureter was found. Then, the cleavage was advanced from the ureter to the renal hilus with sharp and blunt dissections. Renal artery and renal vein were dissected separately and suspended. The kidney was then mobilized. The Gerota fascia was incised and the mass was identified. The mass was marked with normal parenchyma about 5 mm from its borders and the renal artery was clamped with a bulldog clamp. Then the mass was completely dissected. The tumor bed was sutured with 3/0 V‐Loc sutures. The outer suturation was made with 0 Vicryl sutures and clips. The Bulldog clamp was opened. After hemostasis, a Jackson‐Pratt drain was placed into the surgery region. The skin and subcutaneous layers were closed and the operation was terminated.

2.2.2. Laparoscopic partial nephrectomy

Following the initiation of general anesthesia, a 16 Fr foley and nasogastric catheter were introduced. Transperitoneal approach was employed in all of the cases. The abdomen was entered with a veress needle and inflated in a 60° lumbotomy position. Then, two 11‐inch and one 5‐inch ports were inserted. Then the colon was mobilized from the Toldt line. The kidney was reached via entering the retroperitoneal area. The kidney was spared from the surrounding tissues by sharp and blunt dissections. Renal hilus was identified and mass was reached. The mass was excised by cutting with scissors with a 0.5 cm normal tissue margin. Hemostasis was achieved with Surgicel or Floseal. Then, the mass was taken out with the Endo Catch specimen bag. A Jackson‐Pratt drain was placed into the surgery region. The 11‐inch ports were closed with 0 vicryl suture. The skin was closed subcuticular with 4‐0 Vicryl and the procedure was terminated.

2.3. Statistical analysis

Propensity score matching was performed for the standardization of the confounding factors in the study group. Multivariate logistic regression was used to calculate the propensity score of each patient according to patient and mass characteristics. According to the calculated propensity score, patients who underwent LPN were matched with patients who underwent RAPN with similar scoring.

Patients’ data were compared with Student's t test. Mann‐Whitney U test and Chi‐square test were used for comparison of continuous variables and categorical variables, respectively. Parametric variables were defined as mean ± SD and nonparametric variables were defined as median and interquartile range. Univariate and multivariate analyses were performed to determine the factors predicting renal insufficiency in categories 3 and 4, which were calculated on the basis of the National Kidney Foundation Kidney Disease Outcome Quality Initiative Classification and 5‐year cancer‐specific survival (CSS). Kaplan‐Meier curves and log‐rank test were used to calculate and compare 5‐year overall survival (OS), CSS, and local and distant metastasis rates. All statistical analyses were performed with SPSS 22.0 package program. A P value of less than 0.05 was considered for statistical significance.

3. RESULTS

Each of the RAPN and LPN groups included 71 patients. There were more right‐sided tumors in the RAPN group (P = 0.014). Furthermore, the RAPN group included more complex tumors; there were fewer exophytic and more hilar tumors in this group (P = 0.022). Other demographic characteristics were similar between the groups. Demographic data and tumor characteristics of the patients are shown in Table 1.

Table 1.

Comparison of patient and tumor characteristics

Variables	RAPN (n = 71)	LPN (n = 71)	P value
Gender			0.486
Female	31 (43.6)	34 (47.8)
Male	40 (56.4)	37 (52.2)
Age	52.9 ± 11.8	54.6 ± 12.4	0.697
BMI (kg/m2)	24.5 ± 4.2	23.8 ± 3.1	0.412
Follow‐up period (mo.)	58.11 ± 12.81	64.82 ± 11.18	0.588
The accompanying comorbidities
Hypertension	21 (29.5)	18 (25.3)	0.282
Diabetes mellitus	9 (12.6)	11 (15.5)	0.819
Serum creatinine (mg/mL)	0.88 (0.76‐1.12)	0.92 (0.81‐1.08)	0.602
eGFR (mL/min/1.73 m2)	82.6 ± 18.1	84.9 ± 21.4	0.294
Tumor diameter (cm)	2.48 ± 1.12	2.79 ± 1.18	0.681
Tumor side			0.014
Left	28 (38.0)	41 (66.1)
Right	44 (62.0)	39 (33.9)
Tumor location			0.022
Exophytic	23 (32.4)	33 (46.4)
Mesophytic	26 (36.6)	24 (33.8)
Endophytic	12 (16.9)	12 (16.9)
Hilar	10 (14.1)	2 (2.8)

Abbreviations: BMI, body‐mass index; eGFR, estimated glomerular filtration rate; LPN, laparoscopic partial nephrectomy; RAPN, robotic‐assisted partial nephrectomy.

Values are given as mean ± SD, number (%) or median (range).

Significant P values are given in bold and italics.

The mean WIT in the RAPN group was shorter (P = 0.019). At the postoperative 12th month, new onset stage 3 and 4 renal insufficiencies were observed at the same rates in both groups (4.2% vs 4.2%). Except these, perioperative and postoperative results were comparable between groups and summarized in Table 2. The mean follow‐up period was 61.38 months (58.11 months for RAPN and 64.82 months for LPN, P = 0.588). There was no significant difference between the two groups in terms of metastasis‐free survival, CSS, and OS rates (P = 0.891, P = 0.710, and P = 0.561, respectively) (Table 3).

Table 2.

Comparison of perioperative and postoperative outcomes

Variables	RAPN (n = 71)	LPN (n = 71)	P value
Warm ischemia time (min)	18.81 ± 10.67	24.39 ± 12.09	0.019
Total operative time (min)	176 (154‐251)	158 (128‐211)	0.524
Estimated blood loss (cc)	210 (100‐385)	240 (120‐330)	0.225
Length of hospital stay (d)	3.2 (2‐5)	3.5 (2‐6)	0.492
Positive surgical margin	2 (2.3)	3 (4.2)	0.184
Transfusion	3 (4.2)	4 (5.6)	0.926
Change of eGFR (mL/min/1.73 m2)	11.38 (4.12‐22.88)	12.39 (3.86‐24.35)	0.641
New onset stage 3 and 4 renal insufficiency	3 (4.2)	3 (4.2)	‐

Abbreviations: eGFR, estimated glomerular filtration rate; LPN, laparoscopic partial nephrectomy; RAPN, robotic‐assisted partial nephrectomy.

Values are given as mean ± SD, number (%) or median (range).

Significant P values are given in bold and italics.

Table 3.

Oncologic outcomes at 5‐year follow‐up after partial nephrectomy

Variables	RAPN (n = 71)	LPN (n = 71)	P value
Follow‐up period (mo.)	58.11 ± 12.81	64.82 ± 11.18	0.588
Metastasis‐free survival	69 (97.1)	68 (95.8)	0.891
Recurrence‐free survival (CSS)	64 (90.1)	61 (85.9)	0.710
Overall survival	59 (82.6)	60 (84.8)	0.561

Abbreviations: CSS, cancer‐specific survival; LPN, laparoscopic partial nephrectomy; RAPN, robotic‐assisted partial nephrectomy.

Values are given as mean ± SD and number (%).

Hypertension, diabetes, and preoperative eGFR were the independent predictive factors for renal insufficiency (P = 0.029, P = 0.013, and P < 0.001, respectively), and preoperative eGFR, WIT, and PSM for 5‐year CSS (P = 0.003, P = 0.015, and P = 0.002, respectively) (Table 4).

Table 4.

Multivariate regression analysis of predictive factors for stage 3 and 4 renal insufficiency and CSS

	Renal insufficiency				Cancer‐specific survival
		95% CI				95% CI
Variables	OR	Lower limit	Upper limit	P value	OR	Lower limit	Upper limit	P value
Age	1.128	0.914	1.138	0.071	1.019	0.892	1.126	0.122
Hypertension	3.116	1.613	13.892	0.029	2.181	1.829	6.359	0.518
Diabetes mellitus	4.691	1.913	12.218	0.013	1.829	0.771	8.129	0.086
Preoperative eGFR	1.298	1.210	1.324	<0.001	1.815	1.792	1.921	0.003
Tumor diameter (cm)	2.254	1.128	9.682	0.088	2.114	0.844	8.738	0.186
Operation method	2.531	0.572	6.319	0.629	2.129	0.328	7.249	0.365
Warm ischemia time (min)	3.218	1.108	9.341	0.819	2.110	2.088	2.217	0.015
Positive surgical margin	1.912	0.461	6.892	0.411	1.625	1.591	1.644	0.002

Abbreviation: eGFR, estimated glomerular filtration rate; CI, confidence interval; OR, odds ratio..

Significant P values are given in bold and italics.

4. DISCUSSION

The wide‐angle use capability of the instruments, three‐dimensional magnified image, and ergonomic facilities which are provided by the robotic platform have allowed the surgeons to confidently apply nephron‐sparing surgery (NSS) to more complex masses and today RAPN has become the preferred operative technique for small, localized renal masses in many centers.14, 15 In our study, patients who underwent RAPN and LPN had similar demographic characteristics, and we found that those underwent RAPN had a shorter WIT than those underwent LPN. In our study, both methods revealed similar 5‐year CSS and OS rates. We have also found that preoperative eGFR is an important predictive factor for both postoperative renal insufficiency and CSS. Baseline eGFR level is an important factor predicting renal insufficiency and CSS after NSS. Likewise, WIT may be a predictive factor as it determines residual kidney quality after surgery. However, the same factors may not be the determining factors for the OS in our cohort. Because, our patient groups were consisted of younger patients and with lower body‐mass index than those in the other reports. In this group of patients, other patient‐related and environmental factors may come into prominence for the 5‐year OS rates. RAPN has been shown to be an important alternative to LPN for NSS.16 However, with the available data, it is not possible to come to a clear conclusion that the RAPN is superior to LPN. In this regard, especially long‐term consequences are limited. There is a strong need for well‐designed studies to compare the important perioperative parameters, such as operation time, estimated blood loss, WIT, length of hospitalization, and analgesic requirement, and postoperative parameters: long‐term functional (creatinine, eGFR) and oncologic outcomes.

Long‐term functional outcomes after minimally invasive NSS are an important issue to be addressed. Kim et al. showed that functional outcomes were better and that postoperative renal function recovery was greater in the RAPN group in their 1.032 disease case series.17

There are conflicting results in the literature about the operation duration of the methods. There are studies showing that RAPN has a shorter operation time, as well as studies showing that there is no significant difference in regards to operation time between the two methods.3, 18 In our study, mean duration of operation was slightly longer in the RAPN group, but there was no significant difference between the two methods. We believe that the cause of these differences that LPN has been practiced in our clinic for many years but RAPN has been applied for the last 6 years. Experience on the technique of the clinic where the procedure is performed and operating surgical team and available equipment in the operating room are important factors affecting the operation time.

WIT is considered to be an important determinant of postoperative renal function, and the general accepted view is that it should not exceed 20 minutes in NSS.19 There are a number of studies in the literature that suggest that RAPN provides a shorter WIT than LPN.5, 18, 20 In these studies, no matching was made between the groups in terms of tumor characteristics by using a nephrometry score. Based on the assumption that RAPN is often reserved for more complex and difficult‐to‐resect tumors, it is possible to say that RAPN provides better perioperative outcomes despite more tumor complexity. In our group, RAPN also provided a shorter WIT in a similar manner. For this reason, we think that RAPN can improve perioperative outcomes.

Important factors predicting postoperative renal insufficiency apart from the applied technique are preoperative eGFR and diseases causing microvessel pathology.21 In our study, we found that presence of hypertension, diabetes, and preoperative eGFR were independent predictors of postoperative renal insufficiency. We found that the method of operation and WIT had no significant effects. Although RAPN leads to shorter WIT, the less remaining parenchyma due to the presence of more complex tumors in this group may be the likely cause.

Masson‐Lecomte et al. compared the outcomes of 220 RAPN and 45 LPN cases in their prospective, multicentered study and found that RAPN was more favorable in terms of WIT, duration of operation, estimated blood loss, hemostatic agent use, and length of hospitalization.18 There was also no significant difference in postoperative creatinine levels and complication rates among the groups. Another comparative study was conducted by Khalifeh et al. with 261 RAPN and 231 LPN cases.20 The authors compared trifecta outcomes, defined as WIT < 25 minutes, negative surgical margin, and no perioperative complications, and all three factors were found to be more favorable in the RAPN group (58.7% vs 31.6%). In our study, there were no significant differences between the groups in terms of estimated blood loss, transfusion, and PSM rates. We think the fact that surgeons performing the cases in other studies have been applying robotic surgery for a long time and they have been more experienced and we have been applying RAPN for the last 6 years although we have been applying LPN for a long time, and our team has little adaptation to robotic instrumentation are effective in these results.

Springer et al. compared the long‐term (5‐year) oncological and functional outcomes of LPN and open partial nephrectomy (OPN) and found no significant difference between the two groups.22 Mellon et al. showed that early oncologic and functional outcomes of RAPN and open PN were similar.23 LPN has proven to provide favorable long‐term oncological outcomes, but the long‐term consequences for RAPN are very limited. First of the two studies reporting midterm oncologic outcomes was conducted by Kyllo et al. and excellent OS (96.8%) and CSS (99.2%) rates were reported after 2.4 years of follow‐up.24 Khalifeh et al. reported 97% OS and 99% CSS rates after 3 years of follow‐up.25 In a recent study, Andrade et al. assessed for the first time the 5‐years long‐term outcome of RAPN and revealed the oncologic reliability of RAPN with similar rates (91.1% OS and 97.8% CSS) to the previous reports of different NSS techniques.26 In our study, the survival rates were slightly lower because the patients had more complications and had a higher mean age. However, in our study, both methods provided similar long‐term survival rates. The oncological results we have obtained support the study of Andrade et al.

Similar long‐term functional and oncological results were obtained despite laparoscopic surgery had been started much time before than the robotic surgery in our clinic and the RAPN treated group harbored more complex tumors. Undoubtedly, the technical advantages brought by the robotic surgery are the most important factors. These results support the view that the robotic approach, as reported by Benway et al., is rather useful for surgeons experienced in laparoscopic surgery as well as for surgeons who do not have sufficient experience in the laparoscopic approach.10

The application of LPN in complex tumors seems limited only to experienced centers because of technical difficulties. Long et al. reported that LPN and RAPN provide similar functional outcomes in 381 patients with a RENAL score of at least 7, but that RAPN carries less risk of conversion to radical nephrectomy.27 There is consensus that both methods are feasible methods for hilar, central, and large complex tumors in experienced hands.28 However, it should be kept in mind that robotic surgery in these tumors may be able to expand their indications for NSS.

An important handicap of the robotic surgery is the cost problem.29 Of course, it is necessary to apply RAPN independently of cost in difficult tumors, for which the laparoscopic surgery is technically difficult to be applied. However, there is a need to support the results of our study with long‐term oncologic and functional outcomes from prospective studies with high‐quality data to perform RAPN in broader indications.

Our study has some limitations. First, although most of the cases were performed by a single surgeon, different surgeons performed operations. The experience of the surgeon is an important factor influencing the outcome of an operation. Second, although we have applied propensity score matching to ensure homogeneity of groups, our study is not a prospective randomized study. In addition, some factors that may affect the outcome, such as the surgeon's learning curve and the intraoperative technique used, were not included in the evaluation. The cost of robotic surgery is also an important issue which should be taken into consideration. It would have been better if we had done a cost analysis in our study and compared the groups in this respect. Another shortcoming of our study may be the fact that the groups have a small number of cases. However, we believe that our study will be a significant contributor to the literature because of the limited data on the long‐term functional and oncological outcomes of RAPN.

5. CONCLUSION

Our study has shown that RAPN provides quite well long‐term (5‐years) oncological and functional outcomes in appropriately selected patients. It is an important alternative to LPN for NSS of complex tumors in particular. Prospective, randomized comparative studies with more cases should clarify the location of RAPN in NSS and the advantages and disadvantages of this technique. Decision to apply whether LPN or RAPN for a renal mass should be determined according to the characteristics of the patient and the tumor, and the experience of the center and the surgeon performing the procedure.

CONFLICT OF INTEREST

The authors have no conflict of interest to report.

Kızılay F, Turna B, Apaydın E, Semerci B. Comparison of long‐term outcomes of laparoscopic and robot‐assisted laparoscopic partial nephrectomy. Kaohsiung J Med Sci. 2019;35:238–243. 10.1002/kjm2.12038